In 1937, Leblond joined the Laboratoire de Synthese Atomique in Paris which was involved in preparing radioactive isotopes for use in investigating the fate of various molecules in biological processes.
Unfortunately, Leblond's first attempt to use autoradiography failed, the reason being that the radioiodine-128 isotope, with its extremely short half-life (25 minutes), disintegrated so quickly that too little radioactivity remained to be detected by the photographic emulsion.
In 1941, Leblond moved to McGill University as a lecturer in histology, and quickly rose to assistant (1943), associate (1946), and then full professor of anatomy (1948).
High Resolution Autoradiography procedure continues to be used today by molecular biologists to detect RNA molecules in situ, and to study the localization of genes and DNA sequences.
Leblond used autoradiography to introduce radioactive precursors of DNA and then examine the renewal and fate of cells of several basic tissue types.
Using mathematical models and modern methods of quantitation, Leblond and his colleagues estimated with remarkable accuracy the turnover and mitotic rates of numerous cell types.
In the male seminiferous epithelium, studies by Leblond and Yves Clermont in the early 1950s had deciphered how spermatogonia gave rise to spermatocytes, which then differentiated into mature sperm cells in a specific cycle.
[17] When Leblond and his colleagues used 14C-bicarbonate, and then 35S-labeled amino acids to investigate protein synthesis, they were astonished to find that virtually all cells in the body incorporated label.
Using radiolabeled cytidine in some forty cell types, he and his colleagues were the first to demonstrate decisively that RNA is continuously synthesized in the nucleus and then migrates to the cytoplasm.
[14][22] In the electron microscope, using the periodic acid silver technique, there was a gradient of staining intensity from the cis to the trans side of the Golgi apparatus, suggesting that carbohydrate residues were added to proteins at this site.
[24][25] Within ten minutes, the label was dramatically localized to the Golgi apparatus of intestinal goblet cells, indicating that this was the cellular site of addition of sugar residues in the synthesis of the carbohydrate side chains of mucous glycoproteins.
Other classics include: identification of how skeletal bones grow through osteoblast deposition and osteoclast remodeling,[26] early discovery of the biogenesis and metabolism of thyroxine[27] and detection of triiodothyronine,[28] early prediction of DNA semiconservative replication[29] published days after the Watson and Crick Nature article,[30] the discovery of axonal transport,[31] the Warshawsky et al.[32] finding that nascent proteins are processed from the rough endoplasmic reticulum through the Golgi apparatus into pancreatic zymogen granules (made in hot competition with the Palade lab at Rockefeller University), the first realization that the Golgi apparatus is the site of terminal glycosylation,[33] the discovery of the cell coat,[34] the cellular biogenesis of collagen,[35] and new insights into the ultrastructure of basement membrane.
This launched a twenty-year molecular exploration culminating in the concept of the basement membrane as an integrated polymer,[36] rather than as layers of separated macromolecules initially favored by others.
He learned to use a computer at age 90, starting a presentation at an international conference back in 2004, by noting: "A month ago, I thought PowerPoint was a tool for sharpening pencils."